Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Objective To investigate the inhibitory effect of toosendanin on the growth of lung adenocarcinoma cells in vitro and in vivo by regulating the expression of cell division cycle associated protein 5(CDCA5).Methods The expression of CDCA5 in different lung tissues was analyzed in TCGA database.The expression level of CDCA5 in BEAS-2B cells and A549 cells was detected by Western blot.The effect of different concentrations of toosendanin on the viability of A549 cells was determined by cell counting kit-8(CCK-8)assay.The A549 cells were randomly divided into 4 groups:control group(normal cells cultured normally),toosendanin group(normal cells cultured with 40 μmol·L-1 toosendanin),toosendanin+pcDNA group(cells transfected with pcDNA empty vector and cultured with 40 μmol·L-1 toosendanin),and toosendanin+CDCA5 group(cells transfected with CDCA5 overexpression vector and cultured with 40 μmol·L-1 toosendanin).After 48 h of cultivation,the proliferation and apoptosis of each group of cells were detected by CCK-8 and flow cytometry,and the expression of proliferation and apoptosis related proteins in each group of cells was detected by Western blot.The BALB/c nude mice were randomly divided into sh-NC and sh-CDCA5 stable transfected cell lines with nude mouse xenograft models.Daily intraperitoneal injection of 0.9％NaCl and 40μmol·L-1 toosendanin solution was given to observe and record the changes in tumor tissue volume and body mass.Results The results of CCK-8 showed that after 48 hours,the survival rates of A549 cells treated with 10,20,30,40,50,60 and 70 μmol·L-1 toosendanin were(80.74±8.71)％,(72.96±6.53)％,(61.01±4.86)％,(51.20±3.13)％,(42.10±5.94)％,(38.93±3.18)％and(33.48±2.94)％,respectively.Toosendanin significantly inhibited the proliferation of A549 cells.The proliferation rates of cells in the control group,toosendanin group,toosendanin+pcDNA group,and toosendanin+CDCA5 group were(100.00±4.19)％,(49.18±6.70)％,(55.75±5.74)％,and(77.66±7.48)％,respectively;the expression levels of CDCA5 protein were 1.08±0.11,0.44±0.04,0.43±0.05 and 0.99±0.10,respectively.The expression levels of CDCA5 protein in tumor tissues of nude mice in the sh-NC group,sh-CDCA5 group,toosendanin+sh-NC group,and toosendanin+sh-CDCA5 group were 1.04±0.14,0.42±0.04,0.56±0.08 and 0.32±0.04,respectively.Compared with the sh-NC group,the tumor blocks formed by nude mice in other groups were significantly smaller,and the tumor volume and weight were significantly lower(all P＜0.05).Compared with the toosendanin+sh-NC group,the toosendanin+sh-CDCA5 group had more significant inhibitory effect on tumor formation,and the difference was statistically significant(P＜0.05).Conclusion Toosendanin can inhibit the growth of lung adenocarcinoma cells in vitro and in vivo,which is mainly related to the inhibition of CDCA5 expression.

Objective To investigate the role of bone marrow mesenchymal stem cells derived from diabetic mice and their paracrine roles in inducing insulin resistance(IR).Methods The mouse model of diabetes mellitus was established,bone marrow mesenchymal stem cells(BMSC)were extracted and cultured,and the culture supernatant(M-BMSC-CS)was collected.(1)Cell experiment:HepG2 hepatocytes were divided into normal low-glycemic culture group[cultured with low-glycemic DMEM(5.55 mmol·L-1)],M-BMSC-CS experimental group(M-BMSC-CS 75 μL),and high-glycemic and high-lipid control group(given 25 mmol·L-1 high-glycemic DMEM+0.25 mmol·L-1 palmitic acid);(2)Animal experiments:Mice were divided into normal mice group(0.9％NaCl by intraperitoneal injection)and M-BMSC-CS-m group(M-BMSC-CS by intraperitoneal injection of normal mice(injection dose 0.2 mL/10 g)].Glucose intake was measured by glucose oxidase method.The fluorescence intensity of Glut2 protein was detected by immunofluorescence.The expression of insulin signaling pathway protein was detected by Western blot.Test oral glucose tolerance(OGTT)and insulin tolerance(ITT).Results The glucose intakes of the normal low-glucose culture group,the M-BMSC-CS experimental group and the high-glucose and high-lipid control group were(2.96±0.05),(1.64±0.28)and(1.42±0.32)mmol·L-1,respectively;the fluorescence expressions of glucose transporter 2(Glut2)were 53.21±2.70,30.95±3.39 and 34.96±7.60,respectively;the protein expression levels of phosphorylated insulin receptor substrate 1-ser307(p-IRS-1ser307)were 0.46±0.21,1.09±0.24 and 0.91±0.16,respectively;phosphorylated protein kinase(p-AKT)protein expression levels were 0.94±0.05,0.59±0.06 and 0.53±0.05;Glut2 protein expression levels were 1.08±0.14,0.58±0.14 and 0.62±0.09,respectively.The above indexes in M-BMSC-CS experimental group were statistically significant compared with those in normal low-glycemic culture group(all P＜0.05).Fasting blood glucose levels in the normal group and M-BMSC-CS-m group were(5.23±0.57)and(9.30±1.14)mmol·L-1;p-AKT protein expression level were 1.27±0.21 and 0.51±0.19;Glut2 protein expression level were 1.17±0.17 and 0.79±0.09,respectively.The above indexes in M-BMSC-CS-m group were significantly different from those in normal mouse group(P＜0.05).Conclusion BMSC culture supernatant from diabetic mice induced insulin resistance of normal HepG2 hepatocytes in vitro and normal mice in vivo.

Objective To study the effect of Hedysarum polysaccharides(HPS)on the expression of transforming growth factor-β,(TGF-β1),smad homologue 3 recombinant protein(smad3)and smad7 in renal tissue of db/db mice with diabetic nephropathy(DN).Methods According to their body weight,6-week-old male db/db mice were randomly divided into 5 groups:model group(0.9％NaCl 0.2 mL·d-1),positive control group(22.75 mg·kg-1·d-1 irbesartan)and experimental-H,-M,-L groups(200,100,50 mg kg-1·d-1 HPS),with 10 mice in each group;another 10 SPF grade male C57BL/6 mice of the same week were selected as normal group(0.9％NaCl 0.2mL·d-1).The mice in the 6 groups were given intragastric administration once a day for 12 weeks.The blood glucose concentration of mice was measured before treatment and at the 4th,8th and 12th week after treatment.The expression levels of TGF-β1,smad3 and smad7 were detected by Western blotting.Results After treatment,the blood glucose levels of the model group was significantly higher than those of the normal group(all P＜0.01);compared with the model group,the levels of blood glucose in the experimental-H,-M groups decreased significantly,and the differences were statistically significant(P＜0.05,P＜0.01).The relative expression levels of TGF-β,protein in normal group,model group,positive control group and experimental-H,-M groups were 0.71±0.16,1.66±0.18,1.00±0.17,0.88±0.15 and 1.23±0.15;the relative expression levels of smad3 protein were 0.89±0.32,2.26±0.35,1.24±0.31,1.05±0.30 and 1.67±0.35;the relative expression levels of smad7 protein were 1.66±0.03,0.60±0.03,1.10±0.07,1.48±0.08 and 0.97±0.09;there were statistically significant differences between the experimental-H,-M groups and the model group(P＜0.05,P＜0.01).Conclusion Hedysarum polysaccharides can improve renal fibrosis and delay the development of diabetic nephropathy by regulating the level of blood glucose,inhibiting TGF-β1,smad3 and increasing the expression of smad7.

Objective To investigate the relationship between the injury and ferroptosis of bone marrow mesenchymal stem cells(BMSCs)induced by high glucose and high fat.Methods BMSCs were divided into normal group(5.50 mmol·L-1 glucose)and high glucose and high fat(HGHF)group(25.00 mmol·L-1 glucose+0.25 mmol·L-1 palmitic acid).Assessment of cellular aging via β-galactosidase staining;enzyme linked immunosorbent assay(ELISA)were used to detect tumor necrosis factor-α(TNF-α),interleukin-10(IL-10)release levels;glutathione(GSH),malondialdehyde(MDA)and ferrous ion(Fe2+)detection kits were used to detect ferroptosis related indicators;Western blotting was used to detect the expression of ferroptosis related signaling pathway protein acyl-CoA synthetase long chain family member 4(ACS14)/arachidonate 15-lipoxygenase(ALOX15)/glutathione peroxidase 4(GPX4).Results The senescence rates of normal group HGHF group were(6.80±1.60)％and(13.00±1.58)％;the levels of TNF-α were(122.54±3.94)and(169.77±2.89)pg·mL-1;the levels of IL-10 were(155.16±3.97)and(105.15±7.30)pg·mL-1;GSH levels were 4.30±0.33 and 1.55±0.14;MDA levels were 2.94±0.10 and 5.84±0.10;Fe2+levels were 6.22±0.35 and 16.13±0.36;the relative expression levels of ACSL4 protein were 0.42±0.05 and 0.84±0.10;the relative ALOX15 protein were 0.61±0.25 and 1.06±0.11;the relative expression levels of GPX4 protein were 1.13±0.17 and 0.33±0.08,respectively.The above indexes in the HGHF group were significantly different from those in the normal group(all P＜0.05).Conclusion 25 mmol·L-1 glucose combined with 0.25 mmol·L-1 palmitic acid for 24 h can be used as a suitable condition to induce BMSCs injury.ferroptosis plays an important role in BMSCs injury induced by high glucose and high fat.

Objective To analyze the influence of target-controlled infusion with different target concentrations of propofol and remifentanil on elderly patients undergoing painless fiberoptic bronchoscopy.Methods Elderly patients undergoing painless fiberoptic bronchoscopy were divided into low-dose group,middle-dose group and high-dose group.Target-controlled infusion with remifentanil and propofol was performed in low-dose group,middle-dose group and high-dose group,and the target effect-site concentrations of remifentanil all were 3.0 ng·mL-1,and the target effect-site concentrations of propofol were 3.0,4.0 and 5.0 μg·mL-1,respectively.The examination began when the target effect-site concentrations of propofol and remifentanil both reached the target concentrations.The anesthesia effect,anesthesia quality(anesthesia time,patient comfort and operator anesthesia satisfaction),recovery time,intubation time and the safety was evaluated.Results The low-dose,middle-dose and high-dose groups included 31,36 and 35 patients,respectively.The excellent and good rate of anesthesia in low-dose group,middle-dose group and high-dose group were 67.74％(21 cases/31 cases),77.78％(28 cases/36 cases)and 82.86％(29 cases/35 cases),respectively.The difference between middle-dose group and high-dose group and low-dose group was statistically significant(all P＜0.05).In the low-dose group,the middle-dose group and the high-dose group,the satisfaction of anesthesia were(6.13±1.19),(7.48±1.25)and(6.50±1.07)min,respectively;the recovery time were(7.01±1.64),(7.58±1.30)and(9.42±1.58)min,respectively;the intubation time were(9.94±2.02),(10.76±1.97)and(13.18±2.25)min,respectively.There were statistically significant differences between low-dose group and middle-dose group and high-dose group(all P＜0.05).The duration of anesthesia in low-dose group,middle-dose group and high-dose group were(31.18±4.26),(29.96±5.08)and(28.74±5.43)min,respectively;the comfort level were(8.95±0.49),(9.03±0.41)and(9.12±0.38)min,respectively;the incidence of hypotension was 12.90％,5.56％and 14.29％;the incidence of physical activity was 16.13％,8.33％and 5.71％;the incidence of cough was 19.35％,13.89％and 11.43％,respectively,The satisfaction of anesthesiologists in the meddle-dose group was significantly higher than that in the low-dose group and the high-dose group,and the differences were statistically significant(all P＜0.05).Conclusion Target-controlled infusion with propofol at a target effect-site concentration of 4.0 μg·mL-1 and remifentanil at a target effect-site concentration of 3.0 ng·mL-1 has the optimal anesthesia quality,the shortest recovery time and intubation time and good safety in elderly patients with painless fiberoptic bronchoscopy.

ObjectiveTo explore the mechanism of treadmill exercise against type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) based on the regulator effects of exercise on ferroptosis. MethodsEight 8-week-old male m/m mice were used as control group (Con, n=8), and db/db mice of the matched age were randomly divided into T2DM model group (db/db, n=8), exercise group (db+Exe, n=8), p38 mitogen-activated protein kinase (MAPK) inhibitor group (db+SB203580, n=8) and exercise combined with p38 MAPK inhibitor group (db+Exe+SB203580, n=8). After one-week adaptive feeding, the mice in the db+Exe group and db+Exe+SB203580 group underwent moderate intensity treadmill exercise for 40 min/d, 5 d/week lasting 8 weeks. The db+SB203580 group and db+Exe+SB203580 group were treated with SB203580 (a specific inhibitor of p38 MAPK) with a dose of 5 mg/kg, 5 d/week for 8 weeks. And the exercise intervention was performed 2 h later after the intraperitoneal injection of SB203580. The body weight and fasting blood glucose of mice were measured regularly every week during the experiment. After 24 h of the last intervention, the mice were weighted, the liver tissues were taken, weighted and the liver index was calculated. The pathological changes of liver were determined by Oil Red O and hematoxylin-eosin (HE) staining. The levels of blood lipids, liver function, Fe²⁺ and oxidative stress markers of liver were measured by enzyme linked immunosorbent assay (ELISA). The related mRNA expression levels of lipogenesis and inflammation were evaluated by quantitative reverse transcriptase-mediated PCR (qRT-PCR). The related protein expression levels of lipogenesis and ferroptosis in liver were determined by immunohistochemical (IHC) staining and Western blot. ResultsThe body weight, fasting blood glucose, liver index, blood lipid and transaminase levels in the db/db group were significantly increased compared with the Con group. HE and Oil Red O staining showed severe lipid accumulation and ballooning change in the liver of db/db mice. Biochemical tests showed that Fe²⁺ and MDA level of liver constitution homogenate increased, while GSH level decreased significantly. The results of qRT-PCR showed that the mRNA levels of MCP-1, IL-6, SREBF1 and ACC1 in liver tissue of db/db mice were all significantly increased. Western blot results showed that the expression levels of SREBF1, ACC1 increased, ferroptosis relative proteins were significantly decreased. The 8 weeks of exercise significantly reduced the rise in body weight, blood glucose, liver index and blood lipid levels in db/db mice. Exercise intervention also alleviated hepatic steatosis and reduced the expression levels of Fe²⁺, MDA, MCP-1, IL-6, ACC1 and SREBF1, upregulated the expression levels of GSH, NRF2, HO-1, SLC7A11 and GPX4 in liver tissue of db/db mice. The intervention of exercise combined with SB203580 significantly down-regulated the mRNA expression levels of ACC1, MCP-1, IL-6, reduced the levels of Fe²⁺ and MDA, and up-regulated the level of GSH in db/db mice. Compared with the db+Exe group, the expression of Fe²⁺, MDA, MCP-1, and SREBF1 in the liver of the db+Exe+SB203580 group mice significantly increased, while the expression level of GSH and expression levels of ferroptosis relative proteins also significantly decreased. In addition, compared with db+SB203580 group, the iron accumulation and lipid peroxidation in the liver of db+Exe+SB203580 group were significantly improved. ConclusionThe8-week treadmill exercise can effectively alleviate liver injury and steatosis, and its mechanism may be related to the inhibition of hepatocyte ferroptosis through p38 MAPK signal.

Objective To study the intervention effect of narrative therapy on non-suicidal self-injury(NSSI),as well as anxiety and depression symptoms in adolescents with depressive disorder.Methods Sixty adolescents with depressive disorder and NSSI were randomly assigned to either the intervention group or the control group using coin flipping.The control group received conventional psychological support,while the intervention group received individual narrative therapy in addition to the conventional psychological support(twice a week,60 minutes per session,for a total of 3 weeks).Assessment of treatment efficacy was conducted using the Adolescent Self-Harm Questionnaire,Children's Depression Inventory,and Children's Anxiety and Mood Scale before the intervention,at the end of the intervention,and one month after the intervention for both groups.Results A total of 26 adolescents in the intervention group and 29 adolescents in the control group completed the entire study.At the end of the intervention and one month after the intervention,the intervention group showed a significant reduction in the NSSI frequency score,NSSI level,anxiety score,and depression score compared to before the intervention(P<0.017).Moreover,at the end of the intervention and one month after the intervention,the intervention group exhibited significantly lower NSSI frequency score,NSSI severity score,NSSI level,anxiety score and depression score compared to the control group(P<0.05).Conclusions Narrative therapy is effective in reducing NSSI frequency and alleviating NSSI severity,as well as anxiety and depression symptoms in adolescents with depressive disorder.[Chinese Journal of Contemporary Pediatrics,2024,26(2):124-130]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.